Throughout this application, various publications are referenced by author and date. Full citations for these publications may be found listed alphabetically at the end of the specification immediately preceding Sequence Listing and the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
Gemfibrozil (GFZ) is a compound that has been utilized as a drug for increasing intracellular accumulation of hydrophilic anionic agents (U.S. Pat. No. 5,422,372, issued Jun. 6, 1995) and as a lipid regulating composition (U.S. Pat. No. 4,859,703, issued Aug. 22, 1989). Gemfibrozil has been shown to be effective in increasing the amount of cholesterol excreted in to bile. (Ottmar Leiss et al., Metabolism, 34(1):74-82 (1985)). Gemfibrozil is described in U.S. Pat. No. 3,674,836 and in The Merck Index, 11 ed., Merck and Co., Inc. Rahway, N.J. 1989; #4280. Gemfibrozil, a drug which therapeutically lowers triglycerides and raises HDL-cholesterol levels, previously has not been reported to have antimicrobial activity. (Brown, 1987; Oliver et al., 1978 and Palmer et al., 1978).
The present invention provides for a method for inhibiting growth of a bacterium which consists essentially of contacting the bacterium with a compound having the structure 
In the compound each of R1,, R2, R3, R4, R5 and R6 may be independently H, F, Cl, Br, I, xe2x80x94OH, xe2x80x94OR7, xe2x80x94CN, xe2x80x94COR7, xe2x80x94SR7, xe2x80x94N(R7)2, xe2x80x94NR7COR8, xe2x80x94NO2, xe2x80x94(CH2)pOR7, xe2x80x94(CH2)pX(R7)2, xe2x80x94(CH2)pXR7COR8, a straight chain or branched, substituted or unsubstituted C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, thioalkyl, methylene thioalkyl, acyl, phenyl, substituted phenyl, or heteroaryl; wherein R7 or R8 may be independently H, F, Cl, Br, I, xe2x80x94OH, xe2x80x94CN, xe2x80x94COH, xe2x80x94SH2, xe2x80x94NH2, xe2x80x94NHCOH, xe2x80x94(CH2)pOH, xe2x80x94(CH2)pX(CH2), xe2x80x94(CH2)pXCOH, a straight chain or branched, substituted or unsubstituted C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkenyl, thioalkyl, methylene thioalkyl, acyl, phenyl, substituted phenyl, or heteroaryl; wherein A may be xe2x80x94N2xe2x80x94, xe2x80x94NHxe2x80x94, xe2x80x94Cxe2x95x90Cxe2x95x90CH2xe2x80x94, xe2x80x94Cxe2x89xa1Cxe2x80x94C2HOHxe2x80x94, xe2x80x94Cxe2x89xa1Cxe2x80x94CH2xe2x80x94, xe2x80x94CH2xe2x80x94CH2Oxe2x80x94, xe2x80x94CH2xe2x80x94CH2xe2x80x94CH2xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94S(xe2x95x90O)2xe2x80x94, xe2x80x94Cxe2x95x90Oxe2x80x94, xe2x80x94Cxe2x95x90Oxe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94Cxe2x95x90Oxe2x80x94, xe2x80x94Cxe2x95x90Oxe2x80x94NHxe2x80x94; and wherein Q, p, n and x may independently be an integer from 1 to 10, or if Q is 1 A may be a (C1-C10)-alkyl chain, (C1-C10)-alkenyl chain or (C1-C10)-alkynyl chain which is branched or unbranched, substituted or unsubstituted and can optionally be interrupted 1 to 3 times by xe2x80x94Oxe2x80x94 or xe2x80x94Sxe2x80x94 or xe2x80x94Nxe2x80x94; or a pharmaceutically acceptable salt or ester thereof, which compound is present in a concentration effective to inhibit growth of the bacterium. In this method, A may be an (C1-C10)-alkylene chain, (C1-C10)-alkyl chain, (C1-C10)-alkenyl chain or (C1-C10)-alkynyl chain which is branched or unbranched, substituted or unsubstituted and can optionally be interrupted 1 to 3 times by xe2x80x94Oxe2x80x94 or xe2x80x94Sxe2x80x94 or xe2x80x94Nxe2x80x94; and wherein the ether linkage to the benzene ring may be alternatively xe2x80x94Sxe2x80x94, xe2x80x94Nxe2x80x94 or xe2x80x94Cxe2x80x94.